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Robust, Chiral, and Porous BINAP-Based Metal–Organic Frameworks for Highly Enantioselective Cyclization Reactions Takahiro Sawano, Nathan C Thacker, Zekai Lin, Alexandra R. McIsaac, and Wenbin Lin J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b09225 • Publication Date (Web): 03 Sep 2015 Downloaded from http://pubs.acs.org on September 3, 2015
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Robust, Chiral, and Porous BINAP-Based Metal–Organic Frameworks for Highly Enantioselective Cyclization Reactions Takahiro Sawano, Nathan C. Thacker, Zekai Lin, Alexandra R. McIsaac, and Wenbin Lin* Department of Chemistry, University of Chicago, 929 E. 57th Street, Chicago, Illinois 60637, United States KEYWORDS (Word Style “BG_Keywords”). If you are submitting your paper to a journal that requires keywords, provide significant keywords to aid the reader in literature retrieval. ABSTRACT: We report here the design of BINAP-based metal-organic frameworks and their postsynthetic metalation with Rh complexes to afford highly active and enantioselective single-site solid catalysts for the asymmetric cyclization reactions of 1,6enynes. Robust, chiral, and porous Zr-MOFs of UiO topology, BINAP-MOF (I) or BINAP-dMOF (II), were prepared using purely BINAP-derived dicarboxylate linkers or by mixing BINAP-derived linkers with unfunctionalized dicarboxylate linkers, respectively. Upon metalation with Rh(nbd)2BF4 and [Rh(nbd)Cl]2/AgSbF6, the MOF precatalysts I•Rh(BF4) and I•Rh(SbF6) efficiently catalyzed highly enantioselective (up to 99% ee) reductive cyclization and Alder-ene cycloisomerization of 1,6-enynes, respectively. I•Rh catalysts afforded cyclization products at comparable enantiomeric excesses (ee’s) and 4-7 times higher catalytic activity than the homogeneous controls, likely a result of catalytic site isolation in the MOF which prevents bimolecular catalyst deactivation pathways. However, I•Rh is inactive in the more sterically encumbered Pauson-Khand reactions between 1,6-enynes and carbon monoxide. In contrast, with a more open structure, Rh-functionalized BINAP-dMOF, II•Rh, effectively catalyzed Pauson-Khand cyclization reactions between 1,6-enynes and carbon monoxide at 10 times higher activity than the homogeneous control. II•Rh was readily recovered and used in Pauson-Khand cyclization reactions for three times without deterioration of yields or ee’s. Our work has expanded the scope of MOF-catalyzed asymmetric reactions and showed that the mixed linker strategy can effectively enlarge the open space around the catalytic active site to accommodate highly sterically demanding polycyclic metallocycle transition states/intermediates in asymmetric intermolecular cyclization reactions. Introduction Metal-organic frameworks (MOFs) are an interesting class of hybrid porous crystalline materials with potential applications in many areas such as gas storage,1 chemical sensing,2 biomedical imaging,2a,3 drug delivery,4 nonlinear optics,5 and catalysis.6,7 MOFs are particularly advantageous over other materials in their versatility as many features, including their functional groups, pore sizes, shapes, and dimensionalities, may be readily fine-tuned.6a In particular, highly efficient and recyclable heterogeneous catalysts have been synthesized by incorporating catalytic sites into the organic bridging ligands.7b,7c,7k In the past few years, the UiO family of MOFs with the Zr6(µ3-O)4(µ3-OH)4 secondary building units (SBUs) and linear dicarboxylate organic linkers have particularly provided an ideal platform for designing highly efficient MOF catalysts because of their stability in a broad range of solvents and under harsh reaction conditions.8 In this context, we recently reported a robust and porous BINAP-MOF of UiO topology and its postsynthetic metalation with Rh- and Rucomplexes to catalyze a range of asymmetric reactions including the 1,4-addition of aryl boronic acids, 1,2-addition of AlMe3, and hydrogenation of ketones and alkenes.7e,9 Although several examples of asymmetric reactions with chiral MOFs have been reported,7f,7h,7j,10 the applications of MOFs in effecting useful asymmetric organic transformations remain a great challenge, in part due to the requirement of large open channels and pores while maintaining the chiral environment around the catalytically active site.
Transition-metal catalyzed cyclization reactions provide an efficient route to complex polycyclic products from simple, readily available acyclic compounds under mild conditions.11 In particular, asymmetric cyclization reactions of 1,6-enynes provide a powerful method to construct chiral carbon-carbon bonds in a stereoselective and atom economical fashion.12 Chiral, five-membered rings resulted from cyclization reactions are important structural components found in a number of natural products and biologically active compounds.13 RhBINAP complexes were found to efficiently catalyze asymmetric intramolecular reactions of 1,6-enynes: Krische and coworkers reported highly effective reductive cyclizations,14 whereas Zhang and coworkers demonstrated highly enantioselective Alder-ene cycloisomerization.15 Rh-BINAP catalysts were also shown by Jeong and coworkers to catalyze asymmetric Pauson-Khand reactions between 1,6-enynes and carbon monoxide.16,17 As transition metal-catalyzed cyclization reactions typically go through rigid polycyclic metallocycle transition states/intermediates, they require significantly more space around the metal centers for the catalytic reactions to proceed. Consequently, MOF catalysts have not been applied to stereoselective cyclization reactions.18 Herein we report the first example of MOF-catalyzed enantioselective cyclization reactions using BINAP-MOF (I) and BINAP-doped MOF (BINAP-dMOF, II) catalysts (Figure 1). We find that Rhfunctionalized BINAP-MOF (I•Rh) readily catalyzed highly enantioselective reductive cyclization and Alder-ene cycloi-
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somerization of 1,6-enynes, but did not catalyze the PausonKhand cyclization between 1,6-enynes and CO. In contrast, BINAP-dMOF•Rh (II•Rh) readily catalyzes Pauson-Khand cyclization reactions between 1,6-enynes and CO with significantly enhanced activity over the homogeneous catalyst. Doping BINAP-derived linkers into the UiO MOF built from a less sterically demanding dicarboxylate linker thus presents a novel strategy for increasing catalytic activities of MOFs: the resultant large open channels not only facilitate substrate/product diffusion but also provide reaction space to accommodate sterically demanding transition states. Ph
Ph P Rh P Ph Ph
BINAP-MOF•Rh (I•Rh)
R
I•Rh(BF4) (1-6 mol%) H 2 (1 atm)
X
Due to the positional disorder and incomplete metalation of the BINAP moiety, investigation of the Rh-coordination environment could not be performed by traditional crystallographic techniques. X-ray absorption fine structure (XAFS) spectroscopy at the Rh K-edge was used to investigate the local coordination environment of Rh in I • Rh(BF4), I • RhCl, Rh(Me2L1)BF4, Rh(Me2L1)Cl, Rh(BINAP)BF4 and [Rh(BINAP)Cl]2. I • Rh(BF4) and Rh(Me2L1)BF4 were fitted with the crystal structure of Rh(BINAP)BF4 (Fig. 2d and Fig.S9–11, SI). I • RhCl was fitted with a monomeric model where the Rh coordination sphere is occupied by BINAP, chloride, and a THF molecule (Fig.2f and Fig.S14, SI). The spectra for Rh(Me2L1)Cl was fitted with the crystal structure of dimeric [Rh(BINAP)Cl]2 (Fig. S12 and Fig. S13, SI). The details of fitting procedures and results are provided in the SI.
BINAP-dMOF•Rh (II•Rh)
Reductive cyclization: R
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X
up to 95% yield up to 99% ee
*
ClCH2Cl2Cl, r.t., 10 h
Me
R = aryl or alkyl X = O or N
Alder-ene cycloisomerization: R
R X
I•Rh(SbF6 ) (0.2-0.5 mol%)
O
CH2Cl2, r.t., 2 h
up to 99% yield up to 99% ee * Et
Et R = aryl or alkyl X = O or N
Pauson-Khand type cycloaddition: R X
R = aryl or alkyl X = O, N, or C
II•RhCl (0.5-3 mol%) cinnamaldehyde 120 °C, 20 h
R up to 80% yield up to 87% ee O
X *
Figure 1. MOF materials as single site solid catalysts for a broad range of asymmetric cyclization reactions. Results and Discussion BINAP-MOF (I) of the framework formula Zr6(OH)4O4(L1)6 was synthesized via our previously published procedure by a solvothermal reaction between 4,4’-bis(4carboxyphenylethynyl)BINAP (H2L1), ZrCl4, and trifluoroacetic acid (TFA) in dimethylformamide (DMF).7e Postsynthetic metalation of I was achieved by addition of 1 equiv Rh(nbd)2BF4 or 0.5 equiv [Rh(nbd)Cl]2 to I (relative to BINAP moieties in I). Inductively-coupled plasma mass spectrometry (ICP-MS) analyses of the Zr:Rh ratios of the digested MOFs afforded Rh loadings of 33% for I•Rh(BF4) and 18% for I•RhCl. Analysis of powder X-Ray diffraction (PXRD) patterns found I maintained its crystallinity after metalation with Rh (Figure 2a).
Figure 2. (a) PXRD patterns of I (simulated from the CIF file, black; freshly prepared I, red), I•Rh(BF4) (blue), and I•Rh(SbF6) (pink). (b) PXRD patterns of freshly prepared I•Rh(BF4) (black), I•Rh(BF4) recovered from reductive cyclization reaction with 1a (red), freshly prepared I•Rh(SbF6) (blue), and I•Rh(SbF6) recovered from Alder-ene reaction with 3a (pink). (c) A comparison of EXAFS data for I•Rh(BF4), Rh(Me2L1)BF4, and Rh(BINAP) BF4. (d) EXAFS data (squares) and best fits (lines) for I•Rh(BF4). Data are displayed in R-space containing both magnitude of Fourier Transform and real components. An R-factor of 0.01 was obtained for the fit. (e) A comparison of EXAFS data for I•RhCl, Rh(Me2L1)Cl, and the [Rh(BINAP)Cl]2 dimer. (f) EXAFS data (squares) and best fits(lines) for I•RhCl. Data are displayed in Rspace containing both magnitude of Fourier Transform and real components. An R-factor of 0.02 was obtained for the fit.
We first explored asymmetric intramolecular cyclization of enynes using I•Rh(BF4). Krische and coworkers reported Rhcatalyzed reductive cyclization using hydrogen as a terminal reductant.14 At 1 mol% I•Rh(BF4) loading (based on Rh), 1,6-
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enyne 1a was converted to monoalkylidene furan 2a in 68% yield and 94% ee in a H2 atmosphere at r. t. (Table 1, entry 1). This cyclization reaction likely proceeded through the rhodacycle as proposed by Krische and coworkers (Table 1). Under similar conditions, the homogeneous control Rh(Me2L1)BF4 was significantly less active affording the cyclized product in only 10% yield and 91% ee (Table 1, entry 2). The enhanced catalytic activity of I•Rh(BF4) over Rh(Me2L1)BF4 (by ~ 7 times) is likely due to the prevention of multi-molecular catalyst deactivation via catalytic site isolation. At 3 mol% loading of I•Rh(BF4), 2a was obtained in nearly quantitative yield and 95% ee (Table 1, entry 3).
er (1g and 1h) were tolerated, giving cyclized products in 83% and 99% yield, respectively (Table 2, entries 7 and 8).
Table 2. Scope of Asymmetric Reductive Cyclization Reaction with I• •Rh(BF4)a
Table 1. Asymmetric Reductive Cyclization of 1,6-Enynesa entry
X
R
Rhloading (mol%)
1
O
4-MeC6H4 (1a)
3
95
95
yield (%)b
ee (%)c
2
O
C6H5 (1b)
3
89
96
3
O
4-MeOC6H4 (1c)
3
87
95
4- BuC6H4 (1d)
3
82
99
4
O
t
5
O
4-CF3C6H4 (1e)
3
70
94
6
O
3,5-Ph2C6H3 (1f)
1
16
88
7
NTs
CH3 (1g)
3
83
67
8
NTs
C6H5 (1h)
6
99
88
a
Reaction conditions: 1 (1 equiv.), catalyst, H2 (1 atm) at r.t. for 10 h. bDetermined by 1H NMR integration with CH3NO2 as an internal standard. cDetermined by chiral HPLC. dCatalyst was generated in situ. Ts = p-toluenesulfonyl
entry
catalyst
Rh-loading (mol%)
1
I•Rh(BF4)
1
68
Rh(Me2L1)BF4
1
10
2
d
3
I•Rh(BF4)
3
yield (%)
95 (90)
b
ee (%)c 94 91
e
95
a
Reaction conditions: 1 (1 equiv.), catalyst, H2 (1 atm) at r.t. for 10 h. bDetermined by 1H NMR integration with CH3NO2 as an internal standard. cDetermined by chiral HPLC. dCatalyst was generated in situ. eIsolated yield.
Next, we examined the substrate scope of 1,6-enynes in the I•Rh(BF4)-catalyzed reductive cyclization reactions (Table 2). 3 mol% of I•Rh(BF4) catalyzed cyclization of the unsubstituted 1,6-enyne 1b to afford monoalkylidene furan 2b in 89% yield and 96% ee (Table 2, entry 2). 1,6-enynes bearing either electron-donating groups or bulky substituents formed cyclic products in high ee’s and good yields (Table 2, entries 3-4). The highest ee of 99% was observed for the cyclized product 2d that bears the bulky tBu group. Electronwithdrawing groups have a slightly deleterious effect on yields due to formation of undesired byproducts; fortunately, the ee remains high for the cyclized product (Table 2, entry 5). For sterically cumbersome substrate 1f, the reaction affords 16% yield, likely attributable to the slow diffusion of 1f through the MOF and/or the limited open space in the MOF (Table 2, entry 6 vs Table 1, entry 1).19 Substrates bearing a nitrogen teth-
The Rh-catalyzed asymmetric Alder-ene cyclization is a powerful method for generating chiral heterocycles possessing the 1,4-diene products from 1,6-enynes. The cyclized product is believed to form via the β-hydride elimination and reductive elimination sequence. While I•Rh(BF4) efficiently catalyzed the reductive cyclization of 1,6-enynes, it was ineffective in the Alder-ene cycloisomerization (Table 3, entry 1). Instead, the I•Rh(SbF6) catalyst, generated in situ by treating I•RhCl with AgSbF6, afforded the cyclized 1,4-diene product in 99% yield and 99% ee (Table 3, entry 2). The less coordinating SbF6- anion is essential for the Alder-ene cyclization activity (Table 3, entry 3). Enhanced activity from site isolation in I•Rh(SbF6) is again demonstrated when comparing the catalytic activity of I•Rh(SbF6) and Rh(Me2L1)(SbF6) (Table 3, entries 2 vs 4); I•Rh(SbF6) is at least 4 times more active than the homogeneous control. We believe that the Rh catalyst is significantly stabilized due to site isolation. The homogenous catalyst is deactivated within two hours and prolonging the reaction time did not lead to increased product formation (Table 3, entries 4 and 5). I•Rh(SbF6)-catalyzed Alder-ene cycloisomerization also has excellent regioselectivity, which is surprising considering the high reactivity of both the starting enyne 3a and the product 4a under catalytic conditions. Zhang and co-workers reported that 1,6-enyne 3a readily isomerized to the 1,5-enyne 3a’ in the presence of high loading of homogeneous catalysts (>20 mol%, Scheme 1).15a Additionally, cycloisomerized product 4a is susceptible to isomerization under prolonged reaction condi-
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tions forming the more stable conjugated 1,3-diene 4a’. Despite the enhanced catalytic activity of I•Rh(SbF6), we did not observe isomerized byproduct 3a’ or 4a’ and only detected 3a and 4a in the 1H NMR spectrum of the crude reaction mixture.
Table 3. Asymmetric Alder-Ene Cyclization of 3aa
O 0.2-0.5 mol% I•RhCl AgSbF6 Et
CH2Cl2, r.t., 2 h
O
Rh
P P
O
*
Me
4a
3a Me
Proposed rhodacycle intermediate in the MOF
entry
Pre-catalyst
Rh loading (mol%)
yield (%)b
ee (%)c
1d
I•Rh(BF4)
0.5
0
–
2
I•Rh(SbF6)
0.2
99 (95)e
99
3d
I•RhCl
0.2
0
–
f
Rh(Me2L1)(SbF6)
0.2
26
99
f,g
Rh(Me2L1)(SbF6)
0.2
26
99
4 5
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loadings, cycloisomerized products 4c and 4d were obtained from para-OMe and para-tBu substituted enyne 3c and 3d in quantitative yields and 99% ee, respectively (Table 4, entries 5 and 6). Enynes bearing electron-withdrawing groups were significantly more reactive; only 0.2 mol% catalyst loading was needed to convert para-CF3 substituted enyne 3e to its cyclized product in quantitative yield and 99% ee in 2 h (Table 4, entry 7). For considerably larger substrate 3f, standard reaction conditions provided only 18% yield; this is likely attributed to sluggish diffusion through the MOF and/or the insufficient open space in the MOF (Table 4, entry 8).20 Substrates bearing a nitrogen tether (1g and 1h) afford cyclized saturated N-heterocycles in excellent enantioselectivity and yields (98% and 99% yield, respectively) (Table 4, entries 9 and 10).15d As was observed with enyne 3a, undesired isomerization or rearrangement was not observed from any of the I•Rh(SbF6)-catalyzed Alder-ene reactions. The PXRD pattern of the recovered I•Rh(BF4) after the reductive cyclization reaction remained similar to that of freshly prepared I•Rh(BF4); this holds true for the recovered I•Rh(SbF6) after the Alder-ene reaction (Figure 2b). These results indicate the framework of I is stable under asymmetric catalytic reaction conditions. However, the recovered I•Rh(BF4) and I•Rh(SbF6) showed low or no catalytic activity when re-subjected to reaction conditions with fresh substrates, suggesting that the BINAP-Rh complexes in the MOF slowly form stable but catalytically inactive species during the catalytic processes. Consistent with this, insignificant amounts of Rh and Zr species were leached from the MOFs as determined by ICP-MS. For the reductive cyclization with I•Rh(BF4), 0.0% Zr and 3.7% rhodium were found in the supernatant. For the Alder-ene reaction with I•Rh(SbF6),
